A Phase 2 Study of VS-6766 Alone and In Combination with Defactinib in Recurrent Low-Grade Serous Ovarian Cancer (LGSOC) (RAMP 201)
- Conditions
- Recurrent Low-Grade Serous Ovarian Cancer (LGSOC)MedDRA version: 21.1Level: PTClassification code 10066697Term: Ovarian cancer recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2020-004264-26-ES
- Lead Sponsor
- Verastem, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Female
- Target Recruitment
- 144
Subjects may be eligible for inclusion in the study if they meet the following criteria:
1. Female subjects >/= 18 years of age
2. Histologically proven LGSOC (ovarian, peritoneal)
a. The Sponsor’s Medical Monitor must review the pathology report prior to the start of treatment
b. Adequate pathology material (as defined in the lab manual) must be available prior to enrollment to be used for central confirmation. Central pathological confirmation does not need to be completed prior to enrollment.
3. Tumor with known KRAS mutational status using a validated testing
method (blood or tissue) prior to treatment assignment. Adequate
archival tumor tissue less than 5 years old or fresh biopsy tissue samples
(as defined in the lab manual) must be available for central confirmation
prior to treatment assignment.
4. Progression (radiographic or clinical) or recurrence of LGSOC after at least one prior systemic therapy for metastatic disease. Below are additional prior treatments that are allowed once the requirement of prior platinum therapy is satisfied.
a. Prior systemic therapy for metastatic disease (FIGO stage II-IV) may
consist of chemotherapy administered as single agent or a platinum or
another chemotherapy doublet with or without bevacizumab, with or
without maintenance therapy or radiation therapy; hormonal therapy;
and/or MEK/RAF inhibitor therapy.
b. Only one prior line of MEK/RAF inhibitor therapy is allowed.
5. Measurable disease according to RECIST 1.1. Measurable disease status must be confirmed by independent radiology review. All radiology studies and confirmation must be performed within 28 days prior to randomization (Part A) or start of study-directed therapy in Part B.
6. An Eastern Cooperative Group (ECOG) performance status
7. Must have adequate organ function defined by the following laboratory parameters:
a. Adequate hematologic function including: hemoglobin [Hb] >/=9.0 g/dL; platelets >/=100,000/mm3; and absolute neutrophil count [ANC] >/=1500/mm3). If a red blood cell transfusion has been administered the Hb must remain stable and >/=9 g/dL for at least 1 week prior to first dose of study therapy.
b. Adequate hepatic function: (i) total bilirubin c. Adequate renal function with creatinine clearance rate of >/=60 mL/min as calculated by the Cockcroft-Gault formula.
d. International normalized ratio (INR) e. Albumin >/=3.0 g/dL (451 µmole/L).
f. Creatine phosphokinase (CPK) g. Adequate cardiac function with left ventricular ejection fraction >/= 50% by echocardiography (ECHO) or multiple-gated acquisition (MUGA) scan.
8. Baseline QTc interval < 460 ms (average of triplicate readings) (CTCAE Grade 1) using Fredericia’s QT correction formula. NOTE: This criterion does not apply to subjects with a right or left bundle branch block.
9. Adequate recovery from toxicities related to prior treatments to at least Grade 1 by CTCAE v 5.0. Exceptions include alopecia and peripheral neuropathy Grade </=2. Subjects with other toxicities that are sta
1. Systemic anti-cancer therapy within 4 weeks of the first dose of study therapy.
2. Co-existing high-grade ovarian cancer or another histology.
3. History of prior malignancy with recurrence <3 years from the time of enrollment. Subjects with basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, and in situ cervical cancer that has undergone potentially curative therapy with no evidence of disease recurrence for =1 year since completion of appropriate therapy may be included. Subjects with other malignancies associated
with very low risk of metastasis or death may be included upon
discussion with the Medical Monitor.
4. Subjects who are deemed in the opinion of their treating physician to be appropriate candidates for a debulking surgery. These subjects should preferentially receive surgery prior to consideration of trial therapy.
5. Major surgery within 4 weeks (excluding placement of vascular access), minor surgery within 2 weeks, or palliative radiotherapy within 1 week (7 days) of the first dose of study therapy.
6. Treatment with warfarin. Subjects on warfarin for DVT/PE can be converted to low-molecular-weight heparin (LMWH) or direct oral anticoagulants (DOACs).
7. Exposure to strong CYP2C9 and CYP3A4 inhibitors or inducers within 7 days prior to the first dose and during the course of therapy. See Table 19 and Table 20 for representative lists of CYP inhibitors and inducers. For additional guidance, see
https://www.fda.gov/drugs/drug-interactions-labeling/drugdevelopment-and-druginteractions-table-substrates-inhibitors-andinducers.
8. Exposure to P-glycoprotein (P-gp) inhibitors or inducers within 14 days prior to the first dose and during the course of the study. See Table 22 for a representative list of Pgp inhibitors and inducers.
9. Symptomatic brain metastases requiring steroids or other interventions. Subjects with previously diagnosed brain metastases are eligible if they have completed their treatment and have recovered from the acute effects of radiation therapy or surgery prior to study entry, have discontinued corticosteroid treatment for these metastases for at least 2 weeks prior to first dose of study therapy, and are neurologically stable, , with no evidence of interim progression. Subjects with new asymptomatic CNS metastases detected during the screening period must receive radiation therapy and/or surgery for CNS metastases. Following treatment, these subjects may then be eligible if all other criteria are met.
10. Known SARS-Cov2 infection (clinical symptoms)
11. For subjects with prior MEK exposure, Grade 4 toxicity deemed related to the MEK inhibitor.
12. Known hepatitis B, hepatitis C or human immunodeficiency virus (HIV) infection that is active and/or requires therapy.
13. Active skin disorder that has required systemic therapy within the past year.
14. History of rhabdomyolysis.
15. Concurrent ocular disorders:
a. Subjects with history of glaucoma, history of retinal vein occlusion (RVO), predisposing factors for RVO, including uncontrolled hypertension, uncontrolled diabetes.
b. Subject with history of retinal pathology or evidence of visible retinal pathology that is considered a risk factor for RVO, intraocular pressure > 21 mm Hg as measured by tonometry, or other significant ocular pathology, such as anatomical abnormalities that increase the risk for RVO.
c. Subjects with a history o
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method